Zfp260, also known as PEX1, is a transcription factor that belongs to the Krüppel family of transcriptional regulators. It plays essential functions in multiple biological processes, including skeletal stem cell maturation and progenitor commitment, cardiac hypertrophy, and extracellular matrix turnover in the heart. It is involved in pathways such as PKC-dependent signaling, α1 -adrenergic signaling, and endothelin-1 signaling [1,2,3,5]. Genetic models, especially KO/CKO mouse models, can be valuable to study its functions.

In skeletal stem cells, Zfp260 is up -regulated during the transition from stem to progenitor stages. Its dysfunction causes lineage arrest at the progenitor stage, impairing bone repair. It maintains chromatin accessibility and regulates Runx2 expression through super -enhancer complexes. Also, PKCα kinase phosphorylates Zfp260 at specific residues crucial for its functional activity [1].

In the heart, knockdown of Zfp260 in cardiomyocytes decreases the response to endothelin -1 and α1 -adrenergic stimulation. Overexpression of Zfp260 can induce cardiomyocyte hypertrophy in vitro and in vivo, and transgenic mice with inducible Zfp260 expression develop cardiac hypertrophy. PEX1 (Zfp260) deficiency increases apoptosis in doxorubicin -induced cardiotoxicity, while overexpression alleviates apoptosis. Additionally, in the heart, Zfp260 overexpression leads to increased fibrosis and up -regulation of fibrotic genes, and its silencing inhibits pro -fibrotic gene expression [2,3,4,5].

In conclusion, Zfp260 is a crucial factor in bone regeneration and cardiac development and function. Model -based research, especially KO/CKO mouse models, has revealed its role in these processes. In bone, it bridges stem cell activation and progenitor cell fate determination. In the heart, it is involved in cardiac hypertrophy, fibrosis, and protection against doxorubicin -induced cardiotoxicity, providing insights into related disease mechanisms.